ZELBORAF 240 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Zelboraf 240mg film-coated tablets

vemurafenib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Zelboraf and what is it used for
2. What you need to know before you take Zelboraf
3. How to take Zelboraf
4. Possible side effects
5. Storage of Zelboraf
6. Contents of the pack and other information

1. What is Zelboraf and what is it used for

Zelboraf is a cancer medicine that contains the active substance vemurafenib. It is used to treat adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery.

It can only be used in patients who have a change (mutation) in a gene called “BRAF”. This change can cause melanoma to develop.

Zelboraf works on the proteins produced from this modified gene and slows down or stops the development of your cancer.

2. What you need to know before you take Zelboraf

Do not takeZelboraf:

if you are allergic to vemurafenib or any of the other ingredients of this medicine (listed in section 6). The symptoms of allergic reactions can include swelling of the face, lips or tongue, difficulty breathing, rash, or feeling dizzy.

Warnings and precautions

Talk to your doctor before starting treatment with Zelboraf.

Allergic reactions

• While taking Zelboraf, you may have allergic reactions, which can be severe.Stop treatment with Zelboraf and seek immediate medical help if you have any of the symptoms of an allergic reaction such as swelling of the face, lips or tongue, difficulty breathing, rash, or feeling dizzy.

Severe skin reactions

• While taking Zelboraf, you may have severe skin reactions. Stop treatment with Zelboraf and consult your doctor immediately if you have a skin rash with any of the following symptoms: blisters on the skin, blisters or sores in the mouth, skin peeling, fever, redness or swelling of the face, hands or soles of the feet.

Previous history of cancer

• Tell your doctor if you have had a different type of cancer, as Zelboraf may cause progression of certain types of cancers.

Radiation treatment reactions

• Tell your doctor if you have received or are going to receive radiotherapy, as Zelboraf may worsen the effects of radiation treatment.

Heart problems

• Tell your doctor if you have a heart problem, such asan alteration in the electrical activity of your heart called “prolonged QT interval”.Your doctor will perform tests to check if your heart is working properly before and during treatment with Zelboraf. If necessary, your doctor may decide to temporarily or permanently stop your treatment with Zelboraf.

Eye problems

• Your doctor should examine your eyes while you are taking Zelboraf.Consult your doctor immediately if you have pain, swelling, redness, blurred vision or other changes in vision while being treated.

Musculoskeletal and connective tissue disorders

• Tell your doctor if you notice any unusual thickening of the palms of your handsalong with tightness of the fingers or unusual thickening of the soles of the feet that could be painful.

Inspect your skin before, during, and after treatment

• If you notice any changes in your skin during the use of this medicine, please consult your doctor as soon as possible.
• Normally during your treatment and up to 6 months after, your doctor will inspect your skin to look for a type of skin cancer called “squamous cell carcinoma”.
• Normally, this lesion appears in areas of the skin damaged by the sun, remains localized, and can be treated with surgery.
• If your doctor diagnoses this type of skin cancer, it will be treated or referred to another doctor for treatment.
• In addition, your doctor needs to examine your head, neck, mouth, lymph nodes, and regularly perform a scan. This is a precautionary measure in case you develop squamous cell carcinoma inside your body. It is also recommended to have a genital examination (for women) and an anal examination before and after finishing treatment.
• While taking Zelboraf, you may develop new melanoma lesions. These lesions are usually removed by surgery and patients continue with their treatment. The control of these lesions is carried out as indicated above for squamous cell carcinoma.

Kidney or liver problems

• Tell your doctor if you have kidney or liver problems. This could affect the activity of Zelboraf. Additionally, your doctor will perform some blood tests to monitor the function of your liver and kidneys before starting treatment with Zelboraf and during treatment.

Sun protection

• If you are taking Zelboraf, you may become more sensitive to sunlight and suffer from sunburn that can be severe. During treatment, avoid exposing your skin directly to the sun's rays.
• If you are going to be exposed to the sun:
• use clothing that protects your skin, including your head and face, arms and legs;
• use a lip protector and a broad-spectrum sunscreen (Sun Protection Factor (SPF) of at least 30, reapplying every two or three hours).
• This will help protect you from sunburn.

Children and adolescents

Zelboraf is not recommended for use in children and adolescents. The effects of Zelboraf in children under 18 years of age are not known.

Other medicines and Zelboraf

Before starting treatment, tell your doctor if you are using or have recently used or may need to use any other medicine.This is very important, as taking more than one medicine at the same time can increase or decrease its pharmacological effect.

Please note that it is important to inform your doctor if you are taking:

• Medicines known to affect the way your heart beats:
• medicines for heart rhythm problems (e.g. quinidine, amiodarone)
• medicines for depression (e.g. amitriptyline, imipramine)
• medicines for bacterial infections (e.g. azithromycin, clarithromycin)
• medicines for nausea and vomiting (e.g. ondansetron, domperidone).
• Medicines that are mainly eliminated by metabolic proteins called CYP1A2 (e.g. caffeine, olanzapine, theophylline) or CYP3A4 (e.g. some oral contraceptives) or called CYP2C8.
• Medicines that interfere with a protein called P-gp or BCRP (e.g. verapamil, cyclosporine, ritonavir, quinidine, itraconazole, gefitinib).
• Medicines that may be affected by a protein called P-gp (e.g. aliskiren, colchicine, digoxin, everolimus, fexofenadine) or by a protein called BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).
• Medicines that stimulate the metabolic proteins called CYP3A4 or the glucuronidation process (e.g. rifampicin, rifabutin, carbamazepine, phenytoin or St. John's Wort).
• Medicines that strongly inhibit the CYP3A4 metabolic protein (e.g. ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, atazanavir).
• A medicine used to prevent blood clots called warfarin.
• A medicine called ipilimumab, another medicine for the treatment of melanoma. The combination of this medicine with Zelboraf is not recommended due to increased liver toxicity.

If you are taking any of these medicines (or if you are not sure), please inform your doctor before taking Zelboraf.

Pregnancy and breastfeeding

• Use an appropriate contraceptive method during treatmentand for at least 6 months after finishing treatment. Zelboraf may reduce the effectiveness of some oral contraceptives. Inform your doctor if you are taking an oral contraceptive.
• Zelboraf is not recommended during pregnancy, unless your doctor considers that the benefit to the mother outweighs the risk to the baby. There is no information on the safety of Zelboraf in pregnant women. Inform your doctor if you are pregnant or plan to become pregnant.
• It is not known whether any of the components of Zelboraf pass into breast milk. Breastfeeding is not recommended during treatment with Zelboraf.

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

Zelboraf has side effects that can affect your ability to drive or use machines. The feeling of fatigue or eye problems may be a reason for you not to drive.

Important information about some of the ingredients of Zelboraf

This medicine contains less than 23 mg of sodium (1mmol) per tablet; this is, essentially “sodium-free”.

3. How to take Zelboraf

Follow the instructions for taking this medicine exactly as indicated by your doctor. If you are unsure, consult your doctor again.

How many tablets should you take

• The recommended dose is 4 tablets twice a day (a total of 8 tablets).
• Take 4 tablets in the morning. Then take 4 tablets in the evening.
• If you notice any side effects, your doctor may reduce the dose to continue treatment. Always take Zelboraf as your doctor has indicated.
• In case of vomiting, continue taking Zelboraf as you normally do and do not take an additional dose.

Take your tablets

• Do not take Zelboraf regularly on an empty stomach.
• Swallow the tablets whole with a glass of water. Do not chew or crush the tablets.

If you take more Zelboraf than you should

If you take more Zelboraf than you should, inform your doctor immediately. Taking more Zelboraf can increase the probability and severity of side effects. No cases of overdose with Zelboraf have been observed.

If you forget to takeZelboraf

• If you forget to take a dose and it is more than 4 hours until the next dose, take the missed dose as soon as you remember. Take the next dose according to your usual schedule.
• If it is less than 4 hours until the next dose, skip the missed dose and continue taking Zelboraf according to your usual schedule.
• Do not take a double dose to make up for missed doses.

If you stop treatment withZelboraf

It is important to take Zelboraf during the prescribed treatment period by your doctor.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Severe allergic reactions

If you suffer from:

• Swelling of the face, lips or tongue
• Difficulty breathing
• Rash
• Feeling of fainting.

Tell your doctor immediately. Do not take any more Zelboraf tablets until you have informed your doctor.

There may be an worsening of radiation side effects in patients treated with radiotherapy before, during, or after treatment with Zelboraf. This can occur in the area treated with radiation, such as the skin, esophagus, gallbladder, liver, rectum, and lungs.

Tell your doctor immediately if you notice any of the following symptoms:

• Rash, blisters, peeling or discoloration of the skin
• Difficulty breathing, which may be accompanied by cough, fever or chills (pneumonitis)
• Difficulty or pain swallowing, chest pain, heartburn or acid reflux (esophagitis).

Please inform your doctor if you notice any changes in your skin as soon as possible.

The following side effects are listed by frequency:

Very common (may affect more than 1 in 10 patients):

• Rash or skin reaction, itching, dry or scaly skin
• Skin disorders including warts
• A type of skin cancer (squamous cell carcinoma)
• Palmoplantar syndrome (i.e. redness, skin peeling or blisters on hands and feet)
• Sunburn, increased sensitivity to sunlight
• Loss of appetite
• Headache
• Changes in taste
• Diarrhea
• Constipation
• Feeling sick (nausea), vomiting
• Hair loss
• Pain in muscles or joints, musculoskeletal pain
• Pain in limbs
• Back pain
• Feeling tired (fatigue)
• Dizziness
• Fever
• Swelling, usually in the legs (peripheral edema)
• Cough

Common (may affect up to 1 in 10 patients):

• Types of skin cancers (basal cell carcinoma, new primary melanoma)
• Thickening of the tissues under the palm of the hand that can cause tightness of the fingers; if severe, it can be disabling
• Inflammation of the eye (uveitis)
• Bell's palsy (a type of facial paralysis that is often reversible)
• Feeling of tingling or burning in hands or feet
• Joint inflammation
• Inflammation of the hair root
• Weight loss
• Inflammation of blood vessels
• Nerve problems that can cause pain, loss of sensation and/or muscle weakness (peripheral neuropathy)
• Changes in liver test results (increased ALT, alkaline phosphatase and bilirubin)
• Changes in heart electrical activity (prolonged QT interval)
• Inflammation of the fatty tissue under the skin
• Abnormal results in kidney blood tests (increased creatinine)
• Changes in liver test results (increased GGT)
• Decreased white blood cell count (neutropenia)
• Low platelet count (thrombocytopenia)
• Mouth pain or mouth sores, inflammation of the mucous membranes (stomatitis)

Uncommon (may affect up to 1 in 100 patients):

• Allergic reactions that can include swelling of the face and difficulty breathing
• Blockage of blood flow to a part of the eye (retinal vein occlusion)
• Pancreatitis
• Changes in liver laboratory test results or liver damage, including severe liver damage to the point where the liver cannot perform its function completely
• A type of cancer (non-cutaneous squamous cell carcinoma)
• Thickening of the deep tissues under the sole of the foot that could be

disabling if severe

Rare (may affect up to 1 in 1,000 patients):

• Progression of pre-existing cancers with RAS mutations (Chronic Myelomonocytic Leukemia, Pancreatic Adenocarcinoma)
• A type of severe skin reaction characterized by rash accompanied by fever and inflammation of internal organs such as liver and kidney
• Inflammatory diseases that mainly affect the skin, lungs, and eyes (sarcoidosis)
• Types of kidney damage characterized by inflammation (acute interstitial nephritis) or damage to the kidney tubules (acute tubular necrosis)

Reporting of side effects

If you experience any side effects, talk to your doctor, even if it is possible side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zelboraf

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date is the last day of the month shown.

Store in the original package to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container contents and additional information

Composition ofZelboraf

• The active ingredient is vemurafenib. Each film-coated tablet contains 240 milligrams (mg) of vemurafenib (in the form of a vemurafenib and succinate acetate hypromellose co-precipitate).
• The other components are:
• Tablet core: anhydrous colloidal silica, sodium croscarmellose, hydroxypropyl cellulose, and magnesium stearate
• Film coating: red iron oxide, macrogol 3350, polyvinyl alcohol, talc, and titanium dioxide.

Appearance of the product and container contents

Zelboraf 240 mg film-coated tablets are white to slightly orange in color. They are oval in shape with the inscription “VEM” engraved on one side.

They are presented in single-dose aluminum blister packs in packs of 56 x 1 tablets.

Marketing authorization holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639

Grenzach-Wyhlen

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the last revision of this prospectus:

Detailed information about this medication is available on the website of the European Medicines Agency: http://www.ema.europa.eu/